title: Coordinated and interactive expression of genes of lipid metabolism and inflammation in adipose tissue and liver during metabolic overload.
abstract: BACKGROUND
  Chronic metabolic overload results in lipid accumulation and subsequent inflammation in white adipose tissue (WAT), often accompanied by non-alcoholic fatty liver disease (NAFLD). In response to metabolic overload, the expression of genes involved in lipid metabolism and inflammatory processes is adapted. However, it still remains unknown how these adaptations in gene expression in expanding WAT and liver are orchestrated and whether they are interrelated.
  
  
  RESULTS
  ApoE*3Leiden mice were fed HFD or chow for different periods up to 12 weeks. Gene expression in WAT and liver over time was evaluated by micro-array analysis. WAT hypertrophy and inflammation were analyzed histologically. Bayesian hierarchical cluster analysis of dynamic WAT gene expression identified groups of genes ('clusters') with comparable expression patterns over time. HFD evoked an immediate response of five clusters of 'lipid metabolism' genes in WAT, which did not further change thereafter. At a later time point (>6 weeks), inflammatory clusters were induced. Promoter analysis of clustered genes resulted in specific key regulators which may orchestrate the metabolic and inflammatory responses in WAT. Some master regulators played a dual role in control of metabolism and inflammation. When WAT inflammation developed (>6 weeks), genes of lipid metabolism and inflammation were also affected in corresponding livers. These hepatic gene expression changes and the underlying transcriptional responses in particular, were remarkably similar to those detected in WAT.
  
  
  CONCLUSIONS
  In WAT, metabolic overload induced an immediate, stable response on clusters of lipid metabolism genes and induced inflammatory genes later in time. Both processes may be controlled and interlinked by specific transcriptional regulators. When WAT inflammation began, the hepatic response to HFD resembled that in WAT. In all, WAT and liver respond to metabolic overload by adaptations in expression of gene clusters that control lipid metabolism and inflammatory processes in an orchestrated and interrelated manner.
authors.affiliation: Department of Metabolic Health Research, TNO (the Netherlands Organization for Applied Scientific Research), Leiden, the Netherlands.
authors.forename: Wen
authors.initials: W
authors.lastname: Liang
authors.forename: Giulia
authors.initials: G
authors.lastname: Tonini
authors.forename: Petra
authors.initials: P
authors.lastname: Mulder
authors.forename: Thomas
authors.initials: T
authors.lastname: Kelder
authors.forename: Marjan
authors.initials: M
authors.lastname: van Erk
authors.forename: Anita M
authors.initials: AM
authors.lastname: van den Hoek
authors.forename: Rob
authors.initials: R
authors.lastname: Mariman
authors.forename: Peter Y
authors.initials: PY
authors.lastname: Wielinga
authors.forename: Michela
authors.initials: M
authors.lastname: Baccini
authors.forename: Teake
authors.initials: T
authors.lastname: Kooistra
authors.forename: Annibale
authors.initials: A
authors.lastname: Biggeri
authors.forename: Robert
authors.initials: R
authors.lastname: Kleemann
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001499:Bayes Theorem; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D007249:Inflammation / Q000209:etiology / Q000378:metabolism*; D050356:Lipid Metabolism / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D008659:Metabolic Diseases / Q000150:complications / Q000503:physiopathology*; D051379:Mice; D046228:Microarray Analysis